Is BCAS2 p.Thr4Ala (c.10A>G) pathogenic?

BCAS2 p.Thr4Ala (c.10A>G) is classified Benign in BCAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-14). AlphaMissense: likely benign (0.0798); Rare (popmax 0.984%, nfe).

How common is BCAS2 p.Thr4Ala (c.10A>G) in the general population?

BCAS2 p.Thr4Ala (c.10A>G) is rare (popmax 0.984%, nfe) (gnomAD).

What do computational predictors say about BCAS2 p.Thr4Ala (c.10A>G)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

BCAS2 p.Thr4Ala

c.10A>G · rs62621917 · VCV779064

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.984%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 13 kb · p 0.004 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.984% European (non-Finnish) · 11,537/1,172,530 alleles

Filtering AF 0.969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.963%

Overall 0.79% 12,638/1,599,124 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.984%	102
Remaining individualsnot grpmax-eligible	0.644%	155
Finnishnot grpmax-eligible	0.528%	189
Admixed American	0.287%	348
African / African-American	0.165%	607
South Asian	0.0773%	1,294
Middle Eastern	0.0595%	1,681
Ashkenazi Jewishnot grpmax-eligible	0.0341%	2,934
East Asian	0.00228%	43,864

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BCAS2
Protein: p.Thr4Ala
Coding: c.10A>G
MANE Select: NM_005872
dbSNP: rs62621917
Type: single nucleotide variant
Location: chr1:114581582 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 26 PDB
Residue 4: a β-strand

Full BCAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS2 p.Ala2Val Uncertain significance ★ ⚠ same type
BCAS2 p.Ala75Val Uncertain significance ★ ⚠ same type
BCAS2 p.Arg222Gln Uncertain significance ★ ⚠ same type
BCAS2 p.Arg76Gln Uncertain significance ★ ⚠ same type
BCAS2 p.Asn123Thr Uncertain significance ★ ⚠ same type
BCAS2 p.Asn133Ser Uncertain significance ★ ⚠ same type
BCAS2 p.Asn220Asp Uncertain significance ★ ⚠ same type
BCAS2 p.Asn48Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bcas2-p-thr4ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown